We have recently shown 3'-5' adenosine-monophosphate (cAMP) and its N6, O2 dibutyryl derivative (dbcAMP) to produce in vitro neurite development, growth and ultrastructural morphologies similar to those elicited by Nerve Growth Factor (NGF). The treatment of cultures with colcemid or cytochalasin B (agents believed to disrupt microtubules and microfilaments, respectively) in the presence of either of the nucleotides or NGF produces equivalent responses. These similarities prompt the speculation that cAMP may in part mediate the actions of NGF. This possibility will be examined by quantitative studies of the effects of phosphodiesterase (PDE) inhibitors and anti-NGF on NGF mediated neuronal development. The endogenous cAMP levels will also be monitored. The effects of cAMP on sympathetic ganglia will be examined. The role of the nucleotide in stimulating in vitro nerve regeneration will be studied by incorporating into the medium a variety of agents including PDE activators and inhibitors, chemicals affecting intracellular Ca ions concentrations, and several of the prostaglandins. The effects of these compounds on the ensuing growth will be evaluated morphologically by differential interference microscopy, and transmission and scanning electron microscopy. The possibility of a neuronal chemotaxis is under study. The effects of cAMP on axoplasmic- flow and on in vivo nerve regeneration will also be investigated. These studies should lead to a more thorough knowledge of nerve maturation and to the eventual development of techniques for enhancing mammalian nerve regeneration.